Longer survival of rat limb allograft. Combined immunosuppression of FK-506 and 15-deoxyspergualin.
We studied the individual and synergistic effect of 3 immunosuppressive drugs, FK-506 (1 mg/kg/day), 15-deoxyspergualin (2.5 mg/kg/day) and cyclosporine (15 mg/kg/day) in a DA/Lewis rat limb allotransplantation model. 74 right hindlimb transplantations were performed. The median time for onset of rejection was 4 days in animals without immunosuppression, 37 days in animals receiving cyclosporine immunosuppression for 30 days, 61 days in animals receiving FK-506 for 30 days, 36 days in animals receiving a 30-day course of cyclosporine and, in the first 15 days, a course of 15-deoxyspergualin, and 76 days in animals receiving a 30-day course of FK-506 and 15-deoxyspergualin in the first 15 days. The combination of cyclosporine with 15-deoxyspergualin did not prolong graft survival and no synergistic effect was evident. In contrast, survival time in rat limb allografts receiving FK-506 and 15-deoxyspergualin was longer than in those receiving single FK-506 therapy. Our findings suggest a positive synergistic immunosuppressive effect with FK-506 and 15-deoxyspergualin in limb allotransplantation.
Muramatsu
K
K
Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, Japan.
Doi
K
K
Akino
T
T
Shigetomi
M
M
Kawai
S
S
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D004357:Drug Synergism; D006085:Graft Survival; D006146:Guanidines / Q000627:therapeutic use*; D006614:Hindlimb / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus; D016559:Tacrolimus